Purpose

In this study, the researchers hope to learn about SGLT2 inhibition on EGP (endogenous glucose production) and plasma glucose concentration in diabetic subjects. Researchers will examine diabetes and the role of increased plasma glucagon, decline in plasma insulin, and fall in plasma glucose concentration.

Condition

Eligibility

Eligible Ages
Between 18 Years and 70 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  1. BMI = 25-35 kg/m^2
  2. must be drug naïve and/or on a stable dose (more than 3 months) of metformin and/or sulfonylurea
  3. HbA1c >7.0% and <10.0%
  4. Other than diabetes, subjects must be in good general health as determined by physical exam, medical history, blood chemistries, CBC, TSH, T4, EKG and urinanalysis.
  5. Only subjects whose body weight has been stable (± 3 lbs) over the preceding three months and who do not participate in an excessively heavy exercise program will be included.

Exclusion Criteria

  1. Presence of significant systemic disease, heart problems including congestive heart failure, unstable angina or acute myocardial infarction, current infectious liver disease, acute stroke or transient ischemic attacks, history of pancreatitis, urosepsis and pyelonephritis, genital mycotic infections, or Type 1 diabetes mellitus
  2. Any hepatic diseases in the past (infectious liver disease, viral hepatitis, toxic hepatic damage, jaundice of unknown etiology) or severe hepatic insufficiency and/or significant abnormal liver function tests defined as aspartate aminotransferase (AST) >3x upper limit of normal (ULN) and/or alanine aminotransferase (ALT) >3x ULN
  3. Renal impairment (e.g., serum creatinine levels ≥1.4 mg/dL for women or ≥1.5 mg/dl for men, or eGFR <60 mL/min/1.73 m2) or history of unstable or rapidly progressing renal disease or end stage renal disease.
  4. Uncontrolled thyroid disease , Cushing's syndrome, congenital adrenal hyperplasia or hyperprolactinemia
  5. Significantly elevated triglyceride levels (fasting triglyceride > 400 mg/dl), uncontrolled increased LDL-C
  6. Untreated or poorly controlled hypertension (sitting blood pressure > 160/95 mm Hg)
  7. Use of anti-obesity drugs or weight loss medications (prescription or OTC) and medications known to exacerbate glucose tolerance (such as isotretinoin, , GnRH agonists, glucocorticoids, anabolic steroids, C-19 progestins) stopped for at least 8 weeks. Use of anti-androgens that act peripherally to reduce hirsutism such as 5-alpha reductase inhibitors (finesteride, spironolactone, flutamide) stopped for at least 4 weeks
  8. Prior history of a malignant disease requiring chemotherapy, prior history of bladder cancer regardless treatment
  9. Patients at risk for volume depletion due to co-existing conditions or concomitant medications, such as loop diuretics should have careful monitoring of their volume status
  10. History of unexplained microscopic or gross hematuria, or microscopic hematuria at visit 1, confirmed by a follow-up sample at next scheduled visit.
  11. Presence of hypersensitivity to dapagliflozin or other SGLT2 inhibitors (e.g. anaphylaxis, angioedema, exfoliative skin conditions
  12. Known hypersensitivity or contraindications to use GLP1 receptor agonists (exenatide, liraglutide)
  13. Use of , thiazolidinediones, GLP-1 receptor agonists, DPP-4 inhibitors, SGLT2 inhibitors stopped for at least 8 weeks.
  14. Eating disorders (anorexia, bulimia) or gastrointestinal disorders
  15. Suspected pregnancy (documented negative serum β-hCG test), desiring pregnancy in next 6 months, breastfeeding, or known pregnancy in last 2 months
  16. Active history of illicit substance abuse or significant intake of alcohol
  17. Having a history of bariatric surgery
  18. Patient not willing to use two barrier method contraception during study period (unless sterilized or have an IUD)
  19. Debilitating uncontrolled psychiatric disorder such as psychosis or neurological condition that might confound outcome variables
  20. Inability or refusal to comply with protocol
  21. Current participation or participation in an experimental drug study in previous three months

Study Design

Phase
Phase 4
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Active Comparator
Byetta / Bydureon
Exenatide: 4 weeks Byetta, 5 to 10ug sc (daily) 12 weeks Bydureon 2mg sc
  • Drug: Exenatide
    Byetta 5 to 10 ug (twice daily) Bydureon 2mg (once weekly)
    Other names:
    • Byetta, Bydureon
Active Comparator
Dapagliflozin
4 weeks Dapagliflozin, Farxiga, 10mg 12 weeks Dapagliflozin, Farxiga, 10mg
  • Drug: Dapagliflozin
    10mg
    Other names:
    • Farxiga
Active Comparator
Byetta/Bydureon plus Dapagliflozin
Exenatide: 4 weeks Byetta, 5 to 10ug sc (daily) 12 weeks Bydureon 2mg sc PLUS Dapagliflozin: 4 weeks Dapagliflozin, Farxiga, 10mg 12 weeks Dapagliflozin, Farxiga, 10mg
  • Drug: Dapagliflozin
    10mg
    Other names:
    • Farxiga
  • Drug: Exenatide
    Byetta 5 to 10 ug (twice daily) Bydureon 2mg (once weekly)
    Other names:
    • Byetta, Bydureon
Placebo Comparator
Placebo
Placebo group (4 weeks and 12 weeks)
  • Drug: Placebo
    Placebo for Dapagliflozin

Recruiting Locations

University of Texas Health Science Center
San Antonio, Texas 78229
Contact:
Eugenio Cersosimo, MD
210-358-7200
cersosimo@uthscsa.edu

More Details

Status
Recruiting
Sponsor
The University of Texas Health Science Center at San Antonio

Study Contact

Eugenio Cersosimo, MD, PhD
210-358-7200
cersosimo@uthscsa.edu

Detailed Description

This study will examine whether the coadministration of exenatide plus dapagliflozin will prevent the increase in EGP and result in an additive or even synergistic decrease in plasma glucose concentration compared to each agent alone.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.